Ursodeoxycholic acid (USCA) appears a unique compound. It is a bile acid of low toxicity which desaturates bile. We have found as well that it has a very high Tm in the rat. However, it may not function well in the process of lipid absorption and, because it may not suppress endogenous bile acid synthesis, it may not extensively displace endogenous bile acid. These latter questions are unresolved. We shall study the effect of UDCA and its taurine conjugate (TUDC) upon cholesterol absorption and endogenous bile acid synthesis in man. In addition we shall study the determinants of the extraodinarily high TM of TUDC in the rat. In the process we shall study the determinants of bile acid Tm in general. Tm reflects the overall rate-limiting step in hepatic bile acid excretion and reflects intimate events occurring at the hepatocyte canalicular membrane. These events have been far less extensively studied than other aspects of transhepatocellular bile acid transport. The effects of UDCA and TUDC upon endogenous bile acid synthesis and cholesterol absorption will be studied using standard isotope and balance techniques. Six patients on a constant 500 mg/da cholesterol intake will be studied for 3 months; one month control, one on UDCA and one TUDC. With the use of 14-C cholesterol and standard sterol balance techniques, we shall quantify endogenous bile acid synthesis and cholesterol absorption. In addition we shall measure cholesterol solubilizing capacity of gallbladder bile before and during UDCA/TUDC administration. In studying Tm, we shall measure binding affinity of various taurine-conjugated bile acids to rat hepatocyte plasma membrane receptors and relate this to uptake kinetics in cultured rat hepatocytes and to Tm measured in the intact animal. By studying various synthetic bile acids, we shall identify those areas on the molecule which influence binding and canalicular excretion rates. Such data will provide the first quantitative assessment of events which determine the rate limiting excretory step in transhepatocyte bile acid transport.